研究动态
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营养学中的亚油酸:水牛大鼠肝脏再生必需的ω-6脂肪酸。

Dietary Linoleic Acid: An Omega-6 Fatty Acid Essential for Liver Regeneration in Buffalo Rats.

发表日期:2023 Aug 31
作者: Robert T Dauchy, Leonard A Sauer, David E Blask
来源: Cellular & Molecular Immunology

摘要:

啮齿动物是目前用于肝脏手术切除研究的最常见动物,这些研究包括肝脏再生、慢性肝病、急性肝衰竭、肝转移、肝功能和肝癌等。我们之前的研究表明,摄入亚油酸(LA)的饮食会刺激啮齿动物和人类肿瘤在体内的生长。在这里,我们比较了3种饮食——5%的玉米油饮食(对照组)、缺乏必需脂肪酸(EFAD)的饮食和EFAD饮食中补充与对照组含量相等的LA(EFAD+LA)。我们假设在EFAD+LA饮食中摄入的LA会提高大鼠的血浆LA水平,并刺激70%肝切除后大鼠的再生,而在EFAD大鼠中则不会发生再生。每个饮食组包括30只雄性和30只雌性的BUFF/CrCrl大鼠。大鼠随意饮食其中之一的饮食,并可自由饮水。在分配的饮食后8周,大鼠进行了70%肝切除术。术后第4天和第21天,在每个饮食组中随机选择30只雄性和30只雌性大鼠进行体内研究,然后处死收集组织样本。体内研究中,从肝脏收集动脉和静脉血样本。与缺乏LA的大鼠相比,具备LA的大鼠的LA、葡萄糖和氧摄取量,以及乳酸和二氧化碳排出量均显著升高。70%肝切除后,对照组和EFAD+LA组的剩余肝脏重量在第4天翻番,达到原始总重量的60%,并在第21天完全再生。然而,EFAD组没有发生再生。在第4天,对照组和EFAD+LA组切除的肝脏部分相比于第21天的肝脏,LA、蛋白质、cAMP和DNA含量显著增加。与LA缺乏组相比,两个具备LA的组中[3H]胸腺嘧啶在肝DNA中的结合明显增加,其中雄性值高于雌性值。这些数据表明,HPX后的肝再生取决于饮食中的LA。了解大鼠LA依赖的肝再生机制支持我们目前在人类中改善手术切除疗法的努力。
Rodents are currently the most common animals used for hepatic surgical resection studies that investigate liver regeneration,chronic liver disease, acute liver failure, hepatic metastasis, hepatic function, and hepatic cancer. Our previous workhas shown that dietary consumption of linoleic acid (LA) stimulates the growth of rodent and human tumors in vivo. Herewe compared 3 diets─a 5% corn oil diet (control), a diet deficient in essential fatty acids (EFAD), and an EFAD supplementedwith LA in amounts equal to those in the control diet (EFAD+LA). We hypothesized that consumption of the LA provided inthe EFAD+LA diet would elevate plasma levels of LA and stimulate regeneration in rats after a 70% hepatectomy (HPX), andthat regeneration would not occur in the EFAD rats. Each diet group was comprised of 30 male and 30 female Buffalo rats(BUFF/CrCrl). Rats were fed one of the 3 diets and water ad libitum. After 8 wk on the assigned diet, rats were underwent a70% HPX. On days 4 and 21 after HPX, 30 male and 30 female rats from each diet group were anesthetized for in vivo studyand then were euthanized for tissue collection. For the in vivo study, arterial and venous blood samples were collected fromthe liver. LA-, glucose-, and O2-uptake, and lactate- and CO2-output were significantly higher in LA-replete rats as comparedwith LA-deficient rats. After a 70% HPX, the remaining liver mass in control and EFAD+LA groups had doubled at day 4,reaching 60% of the original total weight, and had regenerated completely at day 21. However, no regeneration occurred inthe EFAD group. At day 4 the portions of livers removed from the control and EFAD+LA groups had significantly highercontent of LA, protein, cAMP, and DNA as compared with their livers on day 21. [3H]thymidine incorporation into liverDNA was significantly higher in the 2 LA-replete groups, with male values greater than female values, as compared withLA-deficient group. These data indicate that liver regeneration after HPX is dependent on dietary LA. Understanding themechanisms of LA-dependent liver regeneration in rats supports our current efforts to enhance successful surgical resectiontherapies in humans.